In the developing brain, finely specified cell interactions regulate the extensive cell migrations, patterns of cell association, and subsequent synaptic connections which establish the complex neural network. This research proposal concerns the reconstruction of brain tissue from single cells in vitro for detailed investigation of these critical interactions and the spatial, temporal and informational requirements for expression of organotypic patterning. In aggregates formed from selected chick and mouse embryonic brain cell populations, differentiation and cytoarchitectural organization will be analyzed using Golgi impregnation; birthdating and histogenetic mapping will be implemented by autoradiographic labeling; and neuronal-glial relationships and synaptogenesis will be examined by electron microscopy. Histofluorescent, biochemical and pharmacological studies of aggregates reconstituted from brain catecholamine neuron systems will investigate the possible role of catecholamines as developmental cues in processes of cell recognition and self-assembly. Further purification and characterization of tissue-specific histogenetic factors prepared from supernatant media of cultured brain cells will be pursued for effective use as analytical tools in elucidating mechanisms of cell adhesion and directed cell migration. The ultimate goal is the complexing of these specific cell recognition factors to collagen or synthetic matrices to construct coded pre-neural pathways and elicit directed migration of nerve cells according to pre-determined patterns. BIBLIOGRAPHIC REFERENCES: Levitt, P., Moore, R. Y., and Garber, B. B. Selective cell association of catecholamine neurons in brain aggregates in vitro. Brain Research III:311-320. 1976. Palacios, E., Garber, B. B., and Larramendi L. M. H. Neuronal organization of aggregates prepared from chick embryo striatum and entorhinal cortex. Proc. Cajal Club, Am. Assoc. Anat. 1976.